Bacterial heterogeneity

Vision

My long-term goals are to identify genetic and epigenetic heterogeneity in infecting bacteria and investigate the mechanisms driving this inherited diversity and the ones driving its loss. I wish to assess the fitness advantages of different subpopulations, and determine differences in treatment susceptibility among them. My research aims to enhance our understanding of the different states pathogens exist within the host, hopefully contributing to more effective patient treatment and improved therapeutic outcomes by targeting all co-existing subpopulations within an infection.

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Bacterial phenotypic heterogeneity

Heterogeneity is crucial for bacteria to survive stress conditions, combat the host’s immune system and to overcome antibiotic treatments. The research on bacterial heterogeneity often focuses on lab strains under controlled conditions. While such studies have yielded key insights into fundamental bacterial processes, they do not fully capture the complexities of bacterial states within the host or how these states influence pathogen sensitivity to treatments.

 

We developed Microcolony-seq combining experimental and computational tools to analyze clinical samples of bacterial infections, aiming to uncover the bacterial states experienced within the host. I have focused on the Gram-negative Enteropathogenic E. coli (EPEC) and Uropathogenic E. coli (UPEC) from a urinary tract infection and on the Gram-positive Staphylococcus aureus (S. aureus) from a bloodstream infection. By determining the different states using multiple levels, such as the transcriptome, the genome and the fitness advantage of each state, we aim to reveal mechanisms driving bacterial heterogeneity and deepen our understanding of virulence processes linked to this diversity, ultimately improving treatments for life-threatening infections.